The Neutralizing Antibody Scientific Research Support Component will provide essential laboratory and scientific support for CHAVI- by performing high throughput assessments of neutralizing activity against tier 1 and tier 2 reference HlV-1 strains in standardized and validated assays. In addition, we will map the epitopes of broadly neutralizing sera and mAbs, monitor vaccine-elicited nAb responses to identify improved immunogens, adjuvants and vectors, and delineate nAbs as a correlate of protection using breakthrough viruses from phase 2b trials.
Specific Aims Aim 1. To support CHAVI-ID research by defining the magnitude and breadth (M-B) of neutralizing activity in sera from select clinical groups, and by mapping the epitopes of broadly neutralizing sera.
Aim 2. To support CHAVI-ID research by screening memory B cell culture supernatants to identify nAb-producing B cells.
Aim 3. To support CHAVI-ID research by characterizing new mAbs for magnitude and breadth of neutralizing activity and epitope specificity.
Aim 4. To support CHAVI-ID research by monitoring the magnitude and breadth of vaccine-elicited nAbs in animals, human vaccinees, and by assessing vaccine sera neutralization with viruses from vaccine breakthrough infections in humans.

Public Health Relevance

Immunogens that elicit broadly cross-reactive neutralizing antibodies may be important for effective vaccination against HlV-1. Vaccines are the most effective and affordable intervention to control the spread of infectious diseases such as AIDS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
5UM1AI100645-02
Application #
8508875
Study Section
Special Emphasis Panel (ZAI1-JBS-A)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2013
Total Cost
$264,595
Indirect Cost
$96,063
Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Chen, Shuobing; Wu, Jiayi; Lu, Ying et al. (2016) Structural basis for dynamic regulation of the human 26S proteasome. Proc Natl Acad Sci U S A 113:12991-12996
Tian, Ming; Cheng, Cheng; Chen, Xuejun et al. (2016) Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires. Cell 166:1471-1484.e18
Love, Tanzy M T; Park, Sung Yong; Giorgi, Elena E et al. (2016) SPMM: estimating infection duration of multivariant HIV-1 infections. Bioinformatics 32:1308-15
Barton, John P; Goonetilleke, Nilu; Butler, Thomas C et al. (2016) Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable. Nat Commun 7:11660
Astronomo, Rena D; Santra, Sampa; Ballweber-Fleming, Lamar et al. (2016) Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection. EBioMedicine 14:97-111
Herschhorn, Alon; Ma, Xiaochu; Gu, Christopher et al. (2016) Release of gp120 Restraints Leads to an Entry-Competent Intermediate State of the HIV-1 Envelope Glycoproteins. MBio 7:
Theiler, James; Yoon, Hyejin; Yusim, Karina et al. (2016) Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine. Sci Rep 6:33987
Ding, Shilei; Tolbert, William D; Prévost, Jérémie et al. (2016) A Highly Conserved gp120 Inner Domain Residue Modulates Env Conformation and Trimer Stability. J Virol 90:8395-409
Jeffries Jr, T L; Sacha, C R; Pollara, J et al. (2016) The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells. Mucosal Immunol 9:414-27
Abdul-Jawad, Sultan; Ondondo, Beatrice; van Hateren, Andy et al. (2016) Increased Valency of Conserved-mosaic Vaccines Enhances the Breadth and Depth of Epitope Recognition. Mol Ther 24:375-84

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